P1115: A MULTICENTER PHASE 1/2 TRIAL OF EO2463, A MICROBIAL-DERIVED PEPTIDE THERAPEUTIC VACCINE, AS MONOTHERAPY AND IN COMBINATION WITH LENALIDOMIDE AND RITUXIMAB, FOR TREATMENT OF PATIENTS WITH INDOLENT NHL
Authors: P. L. Zinzani, S. M. Ansell, F. Bosch, J. W. Friedberg, J. P. Marolleau, L. Arcaini, R. Garcia-Sanz, A. K. Gopal, C. Grande, R. Merryman, A. Pinto, S. D. Smith, J. C. Villasboas, D. Wallace, J. Fagerberg, J. G. Magalhaes, P. Armand
Journal: HemaSphere (2022)

Background: EO2463 is a therapeutic vaccine designed to activate existing commensal bacteria-specific memory T cells that cross-react with B cell markers in order to drive anti-tumor immune activity against B-cell malignancies. EO2463 contains four microbial-derived, synthetically produced peptides (OMP72, OMP64, OMP65, and OMP66), which correspond to cytotoxic CD8 T cell HLA-A2 restricted epitopes, and exhibit molecular mimicry with the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor), respectively. In pre-clinical models, these peptides can generate strong immune responses and specifically stimulate cross-reactive cytotoxic CD8 T cells to recognize the chosen B cell targets. EO2463 also contains a CD4 helper peptide referred to as universal cancer peptide 2, derived from the human telomerase reverse transcriptase catalytic subunit. The present study is a first-in-human clinical trial of this microbiome-derived peptide therapeutic cancer vaccine approach in patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL). Aims:The primary objectives of the phase 1 part of the trial are to define the recommended phase 2 dose (RP2D) for EO2463 monotherapy, and to confirm the safety of EO2463 at the monotherapy RP2D in combination with lenalidomide (EL), rituximab (ER), and lenalidomide/rituximab (ER2). The primary objective of the phase 2 part of the trial is to estimate the objective response rate (ORR) according to the Lugano Classification 2014 during EO2463 monotherapy Methods: This four-cohort phase 1/2 trial will investigate EO2463 monotherapy, and combinations of EO2463/lenalidomide (EL), EO2463/rituximab (ER), and EO2463/lenalidomide/rituximab (ER2), for treatment of patients with FL and MZL. Cohort 1 is a safety lead-in dose-finding in patients with relapsed/refractory (RR) disease, with a 3-by-3 design to establish the recommended phase 2 dose (RP2D) for EO2463 monotherapy and to confirm the safety of the RP2D for combination schedules of EL, and ER2. Maximal eighteen patients will be included in cohort 1. After the recommended EO2463 monotherapy dose is established, cohorts 2, 3, and 4 will open to accrual. Fifteen patient will be included in each of these cohorts. Cohort 2 will investigate EO2463 monotherapy in patients with newly diagnosed FL/MZL who are not in need of treatment; cohort 3 will investigate EO2463 monotherapy, followed by ER in patients with limited tumor burden who need treatment, and cohort 4 will further investigate EL, followed by ER2 in the RR setting. EO2463 will be administered subcutaneous 4 times at 2-week intervals, followed by continued booster administrations every 4 weeks for 9 (Cohorts 2 and 3) or 12 (Cohorts 1 and 4) months. Inclusion/exclusion criteria, and the design and schedule of the intense immune and safety monitoring will be presented. Results: The safety lead-in dose-finding is currently ongoing, and no safety concerns have been observed thus far. Summary/Conclusion: This is a first in human clinical trial to evaluate safety, determine the recommended phase 2 dose and estimate efficacy of a novel microbial-derived peptide therapeutic vaccine, EO2463, in patients with indolent non-hodgkin lymphoma as monotherapy and in combination with lenalidomide and rituximab.